The Role of the Human Placenta in the Transfer and Metabolism of Insulin*

Abstract

Since 1911 the problem of placental permeability to insulin has been studied sporadically. Carlson, Drennan, Orr and Jones (1, 2) observed that pregnant dogs failed to develop glycosuria after pancreatectomy and concluded that the fetus protected the mother against diabetes, presumably by diaplacental movement of some substance. Other investigators (3, 4), however, were unable to confirm these early studies. Results of work with goats (5), rabbits (6, 7) and mice (8) were variable and suggest that species differences exist in the placental permeability to insulin. By in vitro techniques, systems for the proteolytic inactivation of insulin have been demonstrated in the rat (9) and human placenta (10).This study was undertaken to investigate the role of the human placenta in the transfer and metabolism of insulin in vivo. It was assumed that the placenta handles insulin-I131 as it would unlabeled insulin. METHODTwenty-eight term-pregnant women, 14 to 41 years old, were chosen for this study without regard to parity. No diabetic patients were included. Except for two patients with mild pre-eclampsia (experiments 3 and 7), no complicating diseases were present. Four patients were delivered by elective repeat cesarean section (experiments 3, 7, 15, 16) with TCA due to losses of protein-bound radioactivity by adsorption to glass (10, 11). In subsequent experiments glass adsorption was minimized by using saline containing 0.5 per cent human serum albumin for the dilution of the labeled insulin.Several preparations of insulin-I.31 were analyzed by unidimensional descending chromatography on Munktell 20/150 filter paper (12) in butanol-acetic acid-water (3: 1: 4 or 8.5: 1: 7.5) after being supplemented with unlabeled carrier insulin, sodium iodide, L-monoiodotyrosine (MIT) and L-diodotyrosine (DIT). The iodinated carrier compounds were localized by staining with a solution of ceric sulfate-arsenious acid followed by aniline in acetone (13). Duplicate chromatograms were also sprayed with 0.1 per cent ninhydrin in acetone. The papers were cut into 1-to 2-cm segments and counted in a scintillation well counter. When detectable, the sum of the radioactivity migrating with the mobility of MIT and DIT was less than 1 per cent of the total radioactivity.

ASK1 mediates the teratogenicity of diabetes in the developing heart by inducing ER stress and inhibiting critical factors essential for cardiac development

“…We found that modest hyperglycemia in a type 2 diabetic embryopathy model had lower birth defect incidence than that of type 1 diabetic embryopathy, which has a high degree of hyperglycemia (52). In contrast, insulin may have minimal roles in embryonic development because maternal insulin does not cross the human placenta (1,4,13). Thus, our findings in type 1 diabetes may be extrapolated to conditions of type 2 diabetes.…”

In human gestational diabetes mellitus congenital malformations are related to pre-pregnancy body mass index and to severity of diabetes

“…Insulin was recognised as a teratogen in chicken embryo in 1945 [27]. In the absence of specific antibodies [28], insulin is generally considered not to cross the human placenta [29] but studies do not adequately address early pregnancy. In mammals, moreover, we know that insulin is present in the maternal reproductive tract [30] and that receptors for insulin are present in the embryo as early as the morula stage [30].…”

Peripheral metabolism of insulin, proinsulin, and C-peptide in the pregnant rat.

“…The findings of Buse et al. (18), Wolf et al (19), and Spellacy et al (20) also indicate that the placenta represents a substantial barrier to the transport of insulin in humans. On the other hand, the possibility that the placenta may not be completely impermeable to insulin in the rat (21) as well as in other species (22)(23)(24) has been suggested by other investigators.…”